The vascular necrosis which accompanies Pseudomonas bacteremia leads to wide-spread tissue infarction and provides a continuing intravascular nidus for bacteremia. Histologic section of tissue infected with Pseudomonas shows a striking invasion of vessel tissue in the absence of inflammatory cells. Since this lesion is unique among gram-negative bacteria to Pseudomonas and since mortality in Pseudomonas bacteremia far exceeds that observed in enteric rod bacteremia, it is likely that vascular necrosis is causally related to lethality. The aim of the proposed research is to discover what attracts Pseudomonas so strongly toward vessel walls, why they remain in vessel tissue, and how they cause vascular necrosis. We will examine large numbers of vasculitis-producing strains of P. aeruginosa, with bacteremic strains of E. coli as controls. Specifically we plan to study: (a) the adherence of bacteria to the endothelial and adventitial surfaces of vessels, (b) the bacterial chemoattractant properties of vessel tissue, necrotic tissue, oxygen, acid and enzymic vessel digest. We also will attempt to correlate elastase and exotoxin A and S production by Pseudomonas with the ability to cause vasculitis. An attempt will be made to produce vascular necrosis in small pieces of tissue in vitro in order to determine the importance of a continuous blood supply in the evolution of this lesion. If oxygen is a beter chemoattractant for Pseudomonas than for enteric bacilli under conditions mimicking infection, we will attempt to enhance or abolish vascular accumulation of bacteria in small infected animals in varying ambient p02. We will attempt to elucidate the mechanism by which type-specific and cross-reactive antibody to bacterial lipopolysaccharide protects against Pseudomonas vasculitis. Finally, since thrombosis is a prominent feature of Pseudomonas vasculitis, we plan to study the effect of anticoagulation on survival of agranulocytic animals after Pseudomonas infection.